Comvax

SIDE EFFECTS

In clinical trials involving the administration of 7918
doses of COMVAX to 3561 healthy infants 6 weeks to 15 months of age, COMVAX was
generally well tolerated. In these studies, infants received COMVAX with
licensed pediatric vaccines (n=1745) or investigational vaccines (n=1816).
Serious adverse experience data were available for all 3561 infants and
non-serious adverse experience data were available for a subset of 1678
infants.

Pivotal Immunogenicity And Safety Study

In the pivotal, randomized, multicenter study, 882
infants were assigned in a 3:1 ratio to receive either COMVAX or PedvaxHIB plus
RECOMBIVAX HB at separate injection sites at 2, 4, and 12-15 months of age.
Children may have also received routine pediatric immunizations. The children
were monitored daily for five days after each injection for injection-site and
systemic adverse experiences. During this time, adverse experiences in infants
who received COMVAX were generally similar in type and frequency to those
observed in infants who received PedvaxHIB plus RECOMBIVAX HB.

The most frequently cited events were mild, transient signs
and symptoms of inflammation at the injection site (i.e., pain/soreness,
erythema, and swelling/induration), somnolence, and irritability, all of which
were prompted for on report cards filled out by parents of vaccinated children.
Table 3 summarizes the frequencies of injection-site and systemic adverse
experiences within five days of vaccination that were reported among ≥ 1.0%
of children in this pivotal trial.

Table 3 : Local Reactions and Systemic Complaints
Within 5 Days After Injection Reported to Occur in ≥ 1.0%t of Children
Given a 3-Dose Course of COMVAX Compared to These Events in Children Given
Concomitant Injections of PedvaxHIB and RECOMBIVAX HB

Event

Injection 1‡

Injection 2‡

Injection 3

COMVAX
(N=660)%

PedvaxHIB and RECOMBIVAX HB***
(N=221)%

COMVAX
(N=645)%

PedvaxHIB and RECOMBIVAX HB***
(N=213)%

COMVAX
(N=593)%

PedvaxHIB and RECOMBIVAX HB***
(N=193)%

Injection Site Reactions

Pain/Soreness*

34.5

37.6

24.3

25.8

23.9

21.2

Erythema ( > 1 in.)*

22.4 (2.7)

25.8 (2.7)

25.7 (1.4)

23.5 (3.3)

27.2 (3.0)

24.4 (1.6)

Swelling/Induration ( > 1 in.)*

27.6 (3.0)

33.5 (4.1)

30.4 (2.9)

31.0 (3.8)

27.2 (3.2)

29.5 (4.1)

Systemic Complaints

Irritability*

57.0

46.6

50.7

44.1

32.2

29.0

Somnolence*

49.5

47.1

37.4

31.9

21.1

22.3

Crying

unusual, high pitched*

10.6

8.6

6.7

2.3

2.9

3.6

not otherwise specified

2.3

2.3

1.4

2.3

0.7

1.6

prolonged ( > 4 hrs.)*

2.4

2.3

0.8

1.4

0.2

0

Anorexia

3.9

2.3

2.0

0.9

0.8

0.5

Vomiting

2.1

1.8

2.5

0.9

1.0

1.6

Otitis media

0.5

0

2.0

1.4

2.7

1.6

Fever (°F, rectal equiv.)**

101.0-102.9

14.2

11.9

13.8

12.2

10.5

6.4

≥ 103.0

0.8

0

1.6

1.4

2.7

4.3

Diarrhea

1.7

1.8

0.8

0.9

2.2

0.5

Upper respiratory infection

0.5

0.5

1.1

0.9

1.3

0.5

Rash

0.8

0

0.9

0

0.8

0.5

Rhinorrhea

0.2

0

1.1

0.9

1.3

2.1

Respiratory congestion

0.6

0.5

1.2

0.9

0.3

0.5

Cough

0.2

0

0.9

0.5

0.2

1.0

Candidiasis, oral

0.3

0.5

0.8

0

0.2

0

Rash, diaper

0.5

0.5

0.5

0.9

0.2

0

† Overall frequency of each event listed above is ≥ 1%
even though the frequency after a given dose may be < 1%.
‡ Most children received DTP and OPV concomitantly with the first two doses of
COMVAX or PedvaxHIB and RECOMBIVAX HB.
* Events prompted for on Vaccination Report Card given to parents/guardians of
vaccinees.
** N for injections 1, 2, and 3 equals 655, 639, and 588, respectively, for
COMVAX; N for injections 1, 2, and 3 equals 218, 213, and 187, respectively, for
PedvaxHIB and RECOMBIVAX HB.
*** Injection site reactions for PedvaxHIB and RECOMBIVAX HB based on
occurrence with either of the monovalent components.

Infants Previously Vaccinated With Hepatitis B Vaccine

In a group of infants (N=126) given a three-dose course
of COMVAX after previously receiving a dose of Hepatitis B Vaccine
(Recombinant) at or shortly after birth, the type, frequency, and severity of
adverse experiences did not appear to be greater than those observed in infants
in the pivotal study who did not receive hepatitis B vaccine at birth.

Infants 6 Weeks To 15 Months Of Age

In clinical trials, 3285 doses of COMVAX were
administered to 1678 infants who were monitored for injection-site and systemic
adverse experiences from Days 0 to 5 after each injection of vaccine. Of these,
855 infants had safety data following vaccination at approximately 2 months of
age, 836 infants at approximately 4 months of age and 1573 infants at 12 to 15
months of age. The most frequently reported adverse experiences ( ≥ 1% of
subjects for at least one injection), without regard to causality are listed in
decreasing order of frequency within each body system:

Post-Marketing Experience

As with any vaccine, there is the possibility that broad
use of COMVAX could reveal adverse experiences not observed in clinical trials.
The following additional adverse reactions have been reported with the use of
the marketed vaccine.

Hypersensitivity

Hematologic

Nervous System

Potential Adverse Effects

In addition, a variety of adverse effects have been
reported with marketed use of either PedvaxHIB or RECOMBIVAX HB in infants and
children through 71 months of age. These adverse effects are listed below.

Adverse Event Reporting

Patients, parents and guardians should be instructed to
report any serious adverse reactions to their health-care provider who in turn
should report such events to the U.S. Department of Health and Human Services
through the Vaccine Adverse Event Reporting System (VAERS), 1-800-822-7967. The
healthcare provider should inform the parent or guardian of the National
Vaccine Injury Compensation Program (NVICP), 1-800-338-2382.